CLEC5A Regulates Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality

• DOI: 10.1371/journal.ppat.1002655
• Publication Date: 2012-04-19T20:52:40Z
• Authors: Szu-Ting Chen; Ren-Shyan Liu; Ming-Fang Wu; Yi-Ling Lin; Se-Yi Chen; David Tat-Wei Tan; Teh-Ying Chou; I-Shuen Tsai; Lei Li; Shie-Liang Hsieh
• Keywords: Lethality; Neurotropic virus

CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV)-induced hemorrhagic fever shock syndrome in Stat1⁻/⁻ mice ConA-treated wild type mice. However, whether CLEC5A involved pathogenesis viral encephalitis has not yet been investigated. To investigate role to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb CLEC5A-deficient were generated. We find that Japanese (JEV) directly interacts with induces DAP12 phosphorylation macrophages. In addition, JEV activates secrete proinflammatory cytokines chemokines, which are dramatically reduced JEV-infected Clec5a⁻/⁻ Although blockade cannot inhibit infection neurons astrocytes, inhibits cytokine release from microglia prevents bystander damage neuronal cells. Moreover, causes blood-brain barrier (BBB) disintegrity lethality STAT1-deficient (Stat1⁻/⁻) mice, whereas peripheral administration reduces infiltration virus-harboring leukocytes into central nervous system (CNS), restores BBB integrity, attenuates protects lethality. all surviving develop protective humoral cellular immunity against infection. These observations demonstrate encephalitis, identify as target development new treatments reduce virus-induced brain damage.